Deletion of one allele of Mthfd1 (methylenetetrahydrofolate dehydrogenase 1) impairs learning in mice

Pjetri, Eneda; Zeisel, Steven H.

doi:10.1016/j.bbr.2017.05.051

Cited by 6 publications

(9 citation statements)

References 23 publications

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Section: Resultsmentioning

confidence: 99%

“…Deletion of one allele of Mthfd1 resulted in impaired cue-conditional learning in mice. 36 Finally, enrichment analyses based on reactome pathways revealed a network of pathways related to netrin signalling, which has recently shown to play an important role in synaptic plasticity and memory formation. 37 Next, we also searched for relevant genes in the PFC of recipient's mice that were able to predict the human's donor SCWT using an ML-based variable selection strategy.…”

Section: Gut Microbiotamentioning

confidence: 99%

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Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways

Arnoriaga-Rodríguez

Mayneris‐Perxachs

Contreras‐Rodríguez

et al. 2021

Gut

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BackgroundInhibitory control (IC) is critical to keep long-term goals in everyday life. Bidirectional relationships between IC deficits and obesity are behind unhealthy eating and physical exercise habits.MethodsWe studied gut microbiome composition and functionality, and plasma and faecal metabolomics in association with cognitive tests evaluating inhibitory control (Stroop test) and brain structure in a discovery (n=156), both cross-sectionally and longitudinally, and in an independent replication cohort (n=970). Faecal microbiota transplantation (FMT) in mice evaluated the impact on reversal learning and medial prefrontal cortex (mPFC) transcriptomics.ResultsAn interplay among IC, brain structure (in humans) and mPFC transcriptomics (in mice), plasma/faecal metabolomics and the gut metagenome was found. Obesity-dependent alterations in one-carbon metabolism, tryptophan and histidine pathways were associated with IC in the two independent cohorts. Bacterial functions linked to one-carbon metabolism (thyX,dut, exodeoxyribonuclease V), and the anterior cingulate cortex volume were associated with IC, cross-sectionally and longitudinally. FMT from individuals with obesity led to alterations in mice reversal learning. In an independent FMT experiment, human donor’s bacterial functions related to IC deficits were associated with mPFC expression of one-carbon metabolism-related genes of recipient’s mice.ConclusionThese results highlight the importance of targeting obesity-related impulsive behaviour through the induction of gut microbiota shifts.

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Section: Resultsmentioning

confidence: 99%

Section: Gut Microbiotamentioning

confidence: 99%

Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways

Arnoriaga-Rodríguez

Mayneris‐Perxachs

Contreras‐Rodríguez

et al. 2021

Gut

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“…Additionally, we found no significant difference in tissue levels of folate, indicating that the changes seen are likely to be a response to ineffective gene products and/or to physiological changes in metabolism rather than folate supply. These significant changes in metabolic profile may provide early markers of at-risk individuals who may therefore be protected by appropriate metabolic support, including perhaps folate supplements [12,[87][88][89].…”

Section: Discussionmentioning

confidence: 99%

Folate Related Pathway Gene Analysis Reveals a Novel Metabolic Variant Associated with Alzheimer’s Disease with a Change in Metabolic Profile

Miyan

Buttercase

Beswick³

et al. 2022

Metabolites

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Metabolic disorders may be important potential causative pathways to Alzheimer’s disease (AD). Cerebrospinal fluid (CSF) decreasing output, raised intracranial pressure, and ventricular enlargement have all been linked to AD. Cerebral folate metabolism may be a key player since this is significantly affected by such changes in CSF, and genetic susceptibilities may exist in this pathway. In the current study, we aimed to identify whether any single nucleotide polymorphism (SNPs) affecting folate and the associated metabolic pathways were significantly associated with AD. We took a functional nutrigenomics approach to look for SNPs in genes for the linked folate, methylation, and biogenic amine neurotransmitter pathways. Changes in metabolism were found with the SNPs identified. An abnormal SNP in methylene tetrahydrofolate dehydrogenase 1 (MTHFD1) was significantly predictive of AD and associated with an increase in tissue glutathione. Individuals without these SNPs had normal levels of glutathione but significantly raised MTHFD1. Both changes would serve to decrease potentially neurotoxic levels of homocysteine. Seven additional genes were associated with Alzheimer’s and five with normal ageing. MTHFD1 presents a strong prediction of susceptibility and disease among the SNPs associated with AD. Associated physiological changes present potential biomarkers for identifying at-risk individuals.

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“…Mice were tested at 10–13 weeks in the behavioral battery for locomotor activity and anxiety-like behavior in open field, exploratory behavior in object investigation, anxiety-like behavior in the light-dark box test and learning and memory in fear conditioning test [ 14 ]. In the control group, nine male and ten female mice were tested, while in the L .…”

Section: Methodsmentioning

confidence: 99%

Prenatal exposure to the probiotic Lactococcus lactis decreases anxiety-like behavior and modulates cortical cytoarchitecture in a sex specific manner.

et al. 2020

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Development of the cerebral cortex may be influenced by the composition of the maternal gut microbiota. To test this possibility, we administered probiotic Lactococcus lactis in drinking water to mouse dams from day 10.5 of gestation until pups reached postnatal day 1 (P1). Pups were assessed in a battery of behavioral tests starting at 10 weeks old. We found that females, but not males, exposed to probiotic during prenatal development spent more time in the center of the open field and displayed decreased freezing time in cue associated learning, compared to controls. Furthermore, we found that probiotic exposure changed the density of cortical neurons and increased the density of blood vessels in the cortical plate of P1 pups. Sex-specific differences were observed in the number of mitotic neural progenitor cells, which were increased in probiotic exposed female pups. In addition, we found that probiotic treatment in the latter half of pregnancy significantly increased plasma oxytocin levels in mouse dams, but not in the offspring. These results suggest that exposure of naïve, unstressed dams to probiotic may exert sex-specific long-term effects on cortical development and anxiety related behavior in the offspring.

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Deletion of one allele of Mthfd1 (methylenetetrahydrofolate dehydrogenase 1) impairs learning in mice

Cited by 6 publications

References 23 publications

Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways

Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways

Folate Related Pathway Gene Analysis Reveals a Novel Metabolic Variant Associated with Alzheimer’s Disease with a Change in Metabolic Profile

Prenatal exposure to the probiotic Lactococcus lactis decreases anxiety-like behavior and modulates cortical cytoarchitecture in a sex specific manner.

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